Nicholas Davis, Ph.D.

Nicholas Davis, Ph.D.

Nicholas Davis, Ph.D.

Office Address

 540 E. Canfield, 7322 Scott Hall
Detroit MI 48201

Office Phone

(313) 577-8654
Lab Phone: (313) 577-7807

Office Fax

(313) 577-6739

Biography

The Davis Lab studies the enzymology and cell biology of protein palmitoylation, a reversible, post-translational protein modification in which fatty acyl moieties (typically, the saturated 16-carbon palmitate) are attached to selected protein cysteine residues. Many signaling proteins, including key players in cancer and in synaptic transmission, rely on palmitoylation for tethering to membrane action sites. Palmitoylation is distinguished by its reversibility, with regulated addition and removal dynamically regulating protein association with membranes. Well known examples include H- and N-Ras, where rapid cycles of de- and re-palmitoylation control distribution between Golgi and plasma membranes, as well as the synaptic scaffolding protein PSD-95, where palmitoyl-regulation modulates synaptic strength by controlling receptor numbers at the synapse.

Palmitoylation has proved a difficult study and it is only in the last decade that the mechanisms mediating its addition and removal have begun to emerge. Our entry into this field came in 2002 when we identified a first example palmitoylation enzyme, the yeast protein acyl transferase (PAT) Akr1. This discovery, together with co-discovery of a second yeast PAT, pointed to the larger mammalian protein family that has since emerged as a family of palmitoylation specificities. The PATs of the 23-member human family are now linked to numerous diseases, including many neurological disorders such as Huntington's Disease, mental retardation, and schizophrenia.

Much of our recent work has centered on the development of new proteomic methods for analyzing palmitoylation change. Using this approach we have mapped the seven yeast PATs to cognate substrate proteins and more recently, with improvements to this technology, we have globally tracked the palmitoylation change that accompanies disease progression in a mouse model of Huntington's Disease. We continue to work on palmitoylation in both yeast and brain - mining the yeast genetic system for fundamental mechanisms and in brain, exploring its controlling role in synaptic function and in neurological disease.

Education

Massachusetts Institute of Technology - S.B. - 1978

The Rockefeller University - Ph.D. - 1985

Publications

 J. Wan, J.N. Savas, A.F. Roth, S.S. Sanders, R.R. Singaraja, M.R. Hayden, J.R. Yates, 3rd, and N.G. Davis (2013) Tracking brain palmitoylation change: Predominance of glial change in a mouse model of Huntington's disease. Chemistry & Biology 20: 1421-34.

A.F. Roth, I. Papanayotou, N.G. Davis (2011) The yeast kinase Yck2 has a tripartite palmitoylation signal. Mol Biol Cell 22: 2702-15.

R. Kang, J. Wan, P. Arstikaitis, H. Takahashi, K. Huang, A.O. Bailey, J.X. Thompson, A.F. Roth, R.C. Drisdel, R. Mastro, W.N. Green, J.R. Yates, 3rd, N.G. Davis* and A. El-Husseini* (2008) Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456: 904-9. (*equal contributions)

A.F. Roth, J. Wan, A.O. Bailey, B. Sun, J. Kuchar, W.N. Green, B. Phinney, J.R. Yates, III, and N.G. Davis (2006) Global analysis of protein palmitoylation in yeast. Cell 125: 1003-13.

A.F. Roth, Y. Feng, L. Chen, and N.G. Davis (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J. Cell Biol. 159: 23-28.

Search PubMed for publications from the Davis Lab

Faculty Status

Cell Biology, Neuropharmacology
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Department of Pharmacology